Selective blockade of IGF-IR signaling induces negative biologic effects in ALK⁺ ALCL cells. (A) PPP induces a concentration- and time-dependent decrease in ALK⁺ ALCL cell viability, as measured by exclusion of staining by trypan blue dye at 24 or 48 hours. Importantly, PPP did not induce similar effects on the cell viability of 2 human benign cell types, namely the normal T lymphocytes and the AG01523 cell line that was derived from normal skin fibroblasts. The results represent 2 consistent experiments. (B) PPP (1 μM for 24 hours) also induces a concentration- and time-dependent increase in apoptotic cell death of ALK⁺ ALCL cells, as demonstrated by flow cytometry after staining with annexin V. The results are shown as the mean ± SD of 3 experiments. All treatment points were statistically significant compared with control untreated cells (P < .05). (C) Treating ALK⁺ ALCL cells with PPP (1 μM for 24 hours) induces G₂/M-phase cell-cycle arrest. (D) PPP at 24 hours induces concentration-dependent decrease in the proliferation of ALK⁺ ALCL cells. The decrease in cell proliferation is highly pronounced in SUP-M2 and SR786 cells, with an intermediate effect in Karpas 299 and DEL cells. The results of 3 experiments are shown as mean ± SD. Excluding SU-DHL-1 and DEL cell lines treated with PPP at 1.0 μM, all other treatments were statistically significant compared with control untreated cells (P < .05). (E) Treating ALK⁺ ALCL cell lines with PPP induces a marked decrease in the potential of these cells to form colonies in soft agar. In the left panel, the effects of PPP on SR786 and DEL cell growth are shown as representative examples. Compared with the plates with control nontreated cells, the plates with treated cells show markedly decreased colony formation (P < .001 for SR786 and P < .01 for DEL). As shown in the right panel, the experiments were repeated 3 times, and the results are depicted as the mean ± SD.